Atsuyuki Maeda

Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/mL.

The Lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein (AFP‐L3) has been used as a diagnostic and prognostic marker of hepatocellular carcinoma (HCC). The analytical sensitivity of a conventional method for AFP‐L3% is not sufficient in patients with a low AFP level. This study was performed to determine the clinical utility of a newly developed highly sensitive AFP‐L3% (hs‐AFP‐L3%) assay in patients with an AFP level <20 ng/mL. In the cohort study, serum samples obtained from 270 patients with newly diagnosed HCC before treatment and 396 patients with chronic liver disease at Ogaki Municipal Hospital, in both of which the AFP level was <20 ng/mL, were measured for conventional AFP‐L3% (c‐AFP‐L3%), hs‐AFP‐L3% and des‐gamma‐carboxy prothrombin (DCP). Diagnostic sensitivity and specificity of hs‐AFP‐L3% at a cut‐off level of 5% were 41.5% and 85.1%, respectively, significantly increasing the sensitivity from 7.0% for c‐AFP‐L3%. Multivariate analysis identified hs‐AFP‐L3% as an independent factor associated with reduced long‐term survival. The survival rate of patients with high hs‐AFP‐L3% (≥5%) before treatment was significantly poorer than that of patients with low hs‐AFP‐L3% (<5%) (P < 0.001). In patients with AFP <20 ng/mL, measurements of AFP‐L3% by the highly sensitive method before treatment were more useful for diagnosis and prognosis of HCC than by the conventional method. (Cancer Sci 2011; 102: 1025–1031)

Randomized Phase III Trial of Adjuvant Chemotherapy with Gemcitabine versus S-1 in Patients with Resected Pancreatic Cancer: Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC-01)

A randomized controlled trial has begun in Japan to compare orally administered S-1 with intravenous gemcitabine (GEM) as adjuvant chemotherapy for patients with curatively resected pancreatic cancer. Patients are enrolled within 10 weeks after pancreatectomy to be treated for six months after assignment to either S-1 (80 mg/m(2)/day for four weeks, repeated similarly every six weeks for a total of four courses) or GEM (1000 mg/m(2) on days 1, 8 and 15, repeated similarly every four weeks for a total of six courses). The primary endpoint is overall survival; secondary endpoints include relapse-free survival, incidence of adverse events and health-related quality of life. Each treatment arm includes 180 patients, providing an expected hazard ratio of 0.87 and an upper margin of 1.25 (two-sided alpha-error, 0.05; power, 0.8). Follow-up abdominal computed tomography is repeated every three months during the first two years, then every six months for three years.

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

OBJECTIVE This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. METHODS Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. RESULTS Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. CONCLUSIONS Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).

Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC.

Background: The effectiveness of tumor markers in evaluating outcomes of patients with hepatocellular carcinoma (HCC) remains to be clarified. Summary: The usefulness of the HCC tumor markers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), and des-gamma-carboxy prothrombin (DCP) was reviewed. Elevations in these tumor markers at the time of HCC diagnosis correlate with disease progression as assessed by both imaging studies and pathologic examinations. The combination of these three tumor markers results in good predictive ability for patient survival after diagnosis. In addition, combination at the time of HCC diagnosis of these three tumor markers (as a measure of tumor progression) and serum albumin and bilirubin levels (as indicators of remnant liver function) can be used for HCC staging and further predicts prognosis in patients with HCC. Key Message: The prognosis of patients with HCC can be well discriminated based solely on serum markers. Staging of HCC with serum markers is objective; if stored serum samples are available, HCC stages can be standardized across different countries and time periods.

Omental Flap in Pancreaticoduodenectomy for Protection of Splanchnic Vessels

Intraabdominal bleeding, the most life-threatening complication following pancreaticoduodenectomy (PD), most often is associated with failure of a pancreaticojejunostomy anastomosis or with intraabdominal infection. We investigated whether placement of an omental flap around the splanchnic vessels in PD could reduce the occurrence of intraabdominal bleeding and other postoperative complications. One hundred consecutive patients who underwent PD at the authors’ institution between January 2000 and October 2004 were enrolled in this prospective study. After dissection of the hepatoduodenal ligament, the major splanchnic arteries and the portal vein were covered by the omental flap. Preoperative condition, incidence of pancreatic fistula, intra-abdominal bleeding, other complications, treatment mortality, and hospital stay were analyzed for interrelationships. The frequency of pancreatic fistula (20%) differed little from those in previous reports. However, intraabdominal bleeding was observed in only 1 (1.0%) patient, who was considered to have too thin a flap. No intraabdominal abscess was encountered. No mortality or complications occurred in relation to the omental flap. Thus, wrapping an omental flap around dissected splanchnic vessels in PD reduced postoperative intraabdominal bleeding and infection, but failed to prevent pancreatic fistulas.

Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.

BACKGROUND & AIMS The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often depicts non-hypervascular hypointense hepatic nodules during the hepatobiliary phase in patients with hepatocellular carcinoma (HCC). It is unclear whether the presence of these nodules is associated with HCC recurrence after hepatectomy. We conducted a prospective observational study to investigate the impact of the presence of non-hypervascular hypointense hepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI on the recurrence of HCC after hepatectomy. METHODS A total of 77 patients who underwent hepatectomy for primary, non-recurrent, hypervascular HCC were prospectively followed up after hepatectomy. Post-operative recurrence rates were compared according to the presence of non-hypervascular hypointense nodules on preoperative Gd-EOB-DTPA-enhanced MRI. RESULTS Recurrence rates after hepatectomy were higher in patients with non-hypervascular hypointense nodules (risk ratio 1.9396 [1.3615-2.7222]) and the presence of non-hypervascular hypointense nodules was an independent factor associated with postoperative recurrence (risk ratio 2.1767 [1.5089-3.1105]) along with HCC differentiation and portal vein invasion. While no differences were found in the rate of intrahepatic metastasis recurrence based on the preoperative presence of non-hypervascular hypointense hepatic nodules, the rate of multicentric recurrence was significantly higher in patients with preoperative non-hypervascular hypointense hepatic nodules. CONCLUSIONS Patients with preoperative non-hypervascular hypointense hepatic nodules detected during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI are at higher risk of HCC recurrence after hepatectomy, mainly due to multicentric recurrence.

Evaluation for clinical utility of GPC3, measured by a commercially available ELISA kit with Glypican‐3 (GPC3) antibody, as a serological and histological marker for hepatocellular carcinoma

Aims:  We evaluated the clinical utility of glypican‐3 (GPC3), which has been proposed as a potential novel tumor marker for hepatocellular carcinoma (HCC), as a serological and histological marker for HCC.

Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy

BACKGROUND & AIMS Previous studies reported that the combination of three tumor markers for hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), has the ability to discriminate survival among patients with HCC. In those studies, however, the study population included all patients with various treatment modalities, and tumor markers were measured only before treatment. We investigated the prognostic value of a combination of these tumor markers for HCC, measured before and after treatment, on survival and recurrence in patients treated with hepatectomy. METHODS A total of 173 patients who underwent hepatectomy for primary, non-recurrent HCC were analyzed. Tumor characteristics, postoperative survival, and recurrence rates were compared according to the number of elevated tumor markers measured before and after treatment. RESULTS The correlation between the number of elevated tumor markers before treatment and tumor size, rate of portal vein invasion, and tumor differentiation, respectively, was stronger than that between the number of elevated tumor markers after treatment. In contrast, the number of elevated tumor markers after treatment displayed an excellent ability to discriminate post-treatment survival and recurrence rates compared to that before treatment, and was an independent factor associated with survival and recurrence in multivariate analysis. CONCLUSIONS The combination of tumor markers measured after hepatectomy has a better discriminatory ability for postoperative survival and recurrence in HCC patients treated with hepatectomy in comparison to the combination of tumor markers measured before treatment.

Risk factors of familial pancreatic cancer in Japan: Current smoking and recent onset of diabetes

Objectives: In western countries, 7% to 10% of patients with pancreatic cancer (PC) have a familial predisposition to their disease. The aim of this study was to determine the familial susceptibility to PC in Japan. Methods: Five hundred seventy-seven patients with PC and 577 age- and gender-matched controls were analyzed for cancer history in their first-degree relative(s) (FDRs) and demographic factors. Results: The patients with PC were more likely to have an FDR with PC (6.9%) than the controls (2.9%; odds ratio [OR], 2.5; P = 0.02). Three patients (0.5%), but none of the controls, had a family history of PC in multiple FDRs. Smoking, especially current smoking (OR, 1.5; P = 0.005), and diabetes mellitus (OR: 1.7, P = 0.001) were also associated with PC. The odds increased up to 10-fold if the patients were positive for these 3 factors. The patients with familial PC were more likely to be current smokers (40%) and to have diabetes mellitus (32.5%) than the sporadic cases (30.1% and 20.1%; OR, 1.6 and 1.9). Conclusions: A family history of PC is a risk of PC in Japan (6.9%) as is a personal history of diabetes and smoking. It is prudent to inform the kindred of patients with familiar PC of the risk of smoking and to follow carefully if they develop diabetes.Abbreviations: PC - pancreatic cancer, FDR - first-degree relative, OR - odds ratio, FPC - familial pancreatic cancer, DM - diabetes mellitus, SIR - standardized incidence rate, IPMN - intraductal papillary mucinous neoplasm, MDCT - multidetector computed tomography, US - ultrasound, NFPTR - National Familial Pancreas Tumor Registry

Risk of pancreatitis after endoscopic retrograde cholangiopancreatography and endoscopic biliary drainage

BACKGROUND Pancreatitis is the most common and serious complication to occur after endoscopic retrograde cholangiopancreatography (ERCP). It is often associated with additional diagnostic modalities and/or treatment of obstructive jaundice. The aim of this study was to determine the risk of post-ERCP pancreatitis associated with pancreaticobiliary examination and endoscopic biliary drainage (EBD). METHODS A total of 740 consecutive ERCP procedures performed in 477 patients were analysed for the occurrence of pancreatitis. These included 470 EBD procedures and 167 procedures to further evaluate the pancreaticobiliary tract using brush cytology and/or biopsy, intraductal ultrasound and/or peroral cholangioscopy or peroral pancreatoscopy. The occurrence of post-ERCP pancreatitis was analysed retrospectively. RESULTS The overall incidence of post-ERCP pancreatitis was 3.9% (29 of 740 procedures). The risk factors for post-ERCP pancreatitis were: being female (6.5%; odds ratio [OR] 2.5, P= 0.02); first EBD procedure without endoscopic sphincterotomy (ES) (6.9%; OR 3.0, P= 0.003), and performing additional diagnostic procedures on the pancreatobiliary duct (9.6%; OR 4.6, P < 0.0001). Pancreatitis after subsequent draining procedures was rare (0.4%; OR for first-time drainage 16.6, P= 0.0003). Furthermore, pancreatitis was not recognized in 59 patients who underwent ES. Seven patients with post-EBD pancreatitis were treated with additional ES. CONCLUSIONS Invasive diagnostic examinations of the pancreaticobiliary duct and first-time perampullary biliary drainage without ES were high-risk factors for post-ERCP pancreatitis. Endoscopic sphincterotomy may be of use to prevent post-EBD pancreatitis.